• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5541-5547
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• 2015

Background: The role of surgical resection for patients with single large (${\geq}5cm$) and/or multinodular (${\geq}2$) hepatocellular carcinoma (HCC) is still controversial. This systematic review was performed to evaluate the safety and efficacy of resection for patients with single large and/or multinodular HCC. Materials and Methods: Databases (the PubMed, Web of Science, Embase, and Cochrane databases) were systematically searched to identify relevant studies exploring the safety and efficacy of resection for single large and/or multinodular HCC, published between January 2000 and December 2014. Perioperative morbidity and mortality, overall survival, and disease-free survival of the resection group were calculated. In addition, these outcome variables were also calculated for the control group in the included studies. Results: One randomized controlled trial and 42 nonrandomized studies involving 9,580 patients were eligible for analysis. Eight (1,594 patients) of the 43 studies also reported the outcomes of transarterial chemoembolization (TACE). Although 51.4% of patients featured cirrhosis, 90.7% of them demonstrated Child-Pugh A liver function in the resection group. The median rates of morbidity (24.5%) and mortality (2.5%) after resection were significantly higher than that of TACE (11.0%, P<0.001; 1.9%, P<0.001). However, patients who underwent resection had significantly higher median one-, three-, and five-year overall survival (76.1%, 51.7%, and 37.4%) than those who underwent TACE (68.3%, 31.5%, and 17.5%, all P<0.001). The median 1-, 3-, and 5-year DFS rates after resection were 58.3%, 34.6%, and 24.0%, respectively. Conclusions: Although tumor recurrence after resection for patients with single large and/ or multinodular HCC continues to be a major problem, resection should be considered as a strategy to achieve long-term survival.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2491-2494
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• 2013

Background: To evaluate the relative effectiveness of different treatments of hepatocellular carcinoma (HCC) via the hepatic artery. Materials and Methods: The study sample group consisted of 418 patients who were randomly selected from 2008 to 2012 with a first diagnosis of HCC and treated with transcatheter arterial chemoembolization (TACE) or without (TAE) chemotherapy or transcatheter arterial infusion (TAI). We collected data including tumor size preoperative and one month thereafter to compare change in areas across the three groups, along with various laboratory indexes for comparison. Results: The overall average change of areas was $240.8{\pm}72.1mm^2$. In the three groups it was $265.0{\pm}58.0mm^2$ vs. $250.5{\pm}51.9mm^2$ vs. $123.7{\pm}26.2mm^2$. In groups TACE and TAE values were larger than in group TAI (p<0.01), but the difference between the two was not statistically significant (p= 0.191). Additionally, U/L change of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in groups TACE and TAE was greater than in the TAI cases ($24.0{\pm}13.5$ vs. $20.9{\pm}12.1$ vs. $5.47{\pm}8.20$ and $25.6{\pm}13.5$ vs.$23.2{\pm}12.28$ vs.$5.48{\pm}14.3$) on the preoperative day and two days thereafter (p<0.01). Between the two groups there was no significant cariation (p= 0.320 and p= 0.609). However, the AST and ALT recovered to normal levels one month later on therapy with liver protecting drugs. Conclusion: The groups TACE and TAE demonstrated more effective reduction of tumor size than group TAI. While lipiodol caused acute liver function damage, this proved reversible.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3509-3514
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• 2013

The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson ${\chi}^2$ test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4759-4763
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• 2013

Background: Prognostic factors of postoperative early and late recurrence in patients with hepatocellular carcinoma (HCC) undergoing curative resection remain to be clarified. The aim of this study was to identify risk factors for postoperative early (${\leq}$ 2 year) and late (> 2 year) intrahepatic recurrences in patients with single HCCs without macrovascular invasion. Methods: A total of 280 patients from December 2004 to December 2007 were retrospectively included in this study. Intrahepatic recurrence was classified into early (${\leq}$ 2 year) and late (> 2 year) and the Chi-Square test or Fisher's exact test and multivariate logistic regression analysis were performed to determine significant risk factors. Results: During the follow-up, 124 patients had intrahepatic recurrence, early and late in 82 and 42 patients, respectively. Multivariate logistic regression analysis showed that microvascular invasion (p=0.006, HR: 2.397, 95% CI: 1.290-4.451) was the only independent risk factor for early recurrence, while being female (p = 0.031, HR: 0.326, 95% CI: 0.118-0.901), and having a high degree of cirrhosis (P=0.001, HR: 2.483, 95% CI: 1.417-4.349) were independent risk factors for late recurrence. Conclusions: Early and late recurrence of HCC is linked to different risk factors in patients with single HCC without macrovascular invasion. This results suggested different emphases of strategies for prevent of recurrence after curative resection, more active intervention including adjuvant therapy, anti-cirrhosis drugs and careful follow-up being necessary for patients with relevant risk factors.

• Journal of Ginseng Research
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• v.35 no.1
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• pp.69-79
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• 2011

Hepatocellular carcinoma (HCC) is the fi fth most common malignancy in the world and complicates liver cirrhosis related to hepatitis C virus (HCV) in many cases. We evaluated the therapeutic effect of Korean red ginseng extract (KGE) in patients with chronic liver diseases. Thirty male and female patients with HCC and another thirty with liver cirrhosis were included. Each category was divided into two groups; the first was used as control group, and received medical therapy only and the second group received the medical therapy supplemented with KGE capsules. The treated group with HCC received three KGE capsules/day (900 mg) while the treated group with HCV received two KGE capsules/day (600 mg) for 11 weeks along with their medical therapy. All patients were subjected to clinical examination and laboratory investigations, including liver function tests (at baseline, after 6 weeks of treatment and at the end of the study) and abdominal ultrasonography. Patients showing focal hepatic lesions were subjected to triphasic spiral abdominal computerized tomography and alpha-fetoprotein (AFP). HCV RNA was determined quantitatively by Roche for patients in the HCV group. Results showed that the medical therapy alone failed to normalize the liver enzymes or decrease the virus concentration. KGE administration induced a significant improvement in liver function tests, decreased the tumor marker (AFP) levels, and decreased the viral titers in HCV patients. Thus, KGE demonstrated powerful therapeutic effects against HCV and liver cancer.

• Molecules and Cells
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• v.44 no.9
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• pp.658-669
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• 2021

Enhancers have been conventionally perceived as cis-acting elements that provide binding sites for trans-acting factors. However, recent studies have shown that enhancers are transcribed and that these transcripts, called enhancer RNAs (eRNAs), have a regulatory function. Here, we identified putative eRNAs by profiling and determining the overlap between noncoding RNA expression loci and eRNA-associated histone marks such as H3K27ac and H3K4me1 in hepatocellular carcinoma (HCC) cell lines. Of the 132 HCC-derived noncoding RNAs, 74 overlapped with the eRNA loci defined by the FANTOM consortium, and 65 were located in the proximal regions of genes differentially expressed between normal and tumor tissues in TCGA dataset. Interestingly, knockdown of two selected putative eRNAs, THUMPD3-AS1 and LINC01572, led to downregulation of their target mRNAs and to a reduction in the proliferation and migration of HCC cells. Additionally, the expression of these two noncoding RNAs and target mRNAs was elevated in tumor samples in the TCGA dataset, and high expression was associated with poor survival of patients. Collectively, our study suggests that noncoding RNAs such as THUMPD3-AS1 and LINC01572 (i.e., putative eRNAs) can promote the transcription of genes involved in cell proliferation and differentiation and that the dysregulation of these noncoding RNAs can cause cancers such as HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9487-9494
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• 2014

Background: The size of a hepatic neoplasm is critical for staging, prognosis and selection of appropriate treatment. Our study aimed to compare the radiological size of solid hepatocellular carcinoma (HCC) masses on magnetic resonance imaging (MRI) with the pathological size in a Chinese population, and to elucidate discrepancies. Materials and Methods: A total of 178 consecutive patients diagnosed with HCC who underwent curative hepatic resection after enhanced MRI between July 2010 and October 2013 were retrospectively identified and analyzed. Pathological data of the whole removed tumors wereassessed and differences between radiological and pathological tumor size were identified. All patients were restaged using a modified Tumor-Node-Metastasis (TNM) staging system postoperatively according to the maximum diameter alteration. The lesions were classified as hypo-staged, iso-staged or hyper-staged for qualitative assessment. In the quantitative analysis, the relative pre and postoperative tumor size contrast ratio ($%{\Delta}size$) was also computed according to size intervals. In addition, the relationship between radiological and pathological tumor diameter variation and histologic grade was analyzed. Results: Pathological examination showed 85 (47.8%) patients were overestimated, 82 (46.1%) patients underestimated, while accurate measurement by MRI was found in 11 (6.2%) patients. Among the total subjects, 14 (7.9%) patients were hypo-staged and 15 (8.4%) were hyper-staged post-operatively. Accuracy of MRI for calculation and characterized staging was related to the lesion size, ranging from 83.1% to 87.4% (<2cm to ${\geq}5cm$, p=0.328) and from 62.5% to 89.1% (cT1 to cT4, p=0.006), respectively. Overall, MRI misjudged pathological size by 6.0 mm (p=0.588 ), and the greatest difference was observed in tumors <2cm (3.6 mm, $%{\Delta}size=16.9%$, p=0.028). No statistically significant difference was observed for moderately differentiated HCC (5.5mm, p=0.781). However, for well differentiated and poorly differentiated cases, radiographic tumor maximum diameter was significantly larger than the pathological maximum diameter by 3.15 mm and underestimated by 4.51 mm, respectively (p=0.034 and 0.020). Conclusions: A preoperative HCC tumor size measurement using MRI can provide relatively acceptable accuracy but may give rise to discrepancy in tumors in a certain size range or histologic grade. In pathological well differentiated subjects, the pathological tumor size was significantly overestimated, but underestimated in poorly differentiated HCC. The difference between radiological and pathological tumor size was greatest for tumors <2 cm. For some HCC patients, the size difference may have implications for the decision of resection, transplantation, ablation, or arterially directed therapy, and should be considered in staging or selecting the appropriate treatment tactics.

• IMMUNE NETWORK
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• v.4 no.4
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• pp.237-243
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• 2004

Background: The normal functions of the cell cycle inhibitor p16INK4a are frequently inactivated in many human cancers. Over 80% of hepatocellular carcinoma (HCC) cases lack a functional p16/Rb pathway. p16/Rb pathway, as well as p53 pathway, is considered as one of key components of tumor suppression. Methods: To study the roles of p16INK4a in HCC, a stable cell line expressing exogenous p16 was generated from SNU-449 hepatocellular carcinoma cells lacking endogenous p16, and suppression subtractive hybridization (SSH) was performed in parallel with the control cells. Results: 1) SSH identifies fibronectin (FN1), crystallin ${\alpha}B$ (CRYAB), Rac1, WASP, RhoGEF, and CCT3 as differentially-expressed genes. 2) Among the selected genes, the up-regulation of FN1 and CRYAB was confirmed by Northern blot, RT-PCR and by proteomic methods. Conclusion: These genes are likely to be associated with the induction of stress fiber and stabilization of cytoskeleton. Further studies are required to clarify the possible role of p16 in the signal transduction pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.315-319
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• 2015

Background: Surgical resection of spontaneously ruptured hepatocellular carcinoma (HCC) after successful transarterial embolization (TAE) remains controversial. The aim of this study was to investigate its efficacy in a series of cases. Materials and Methods: We retrospectively examined ruptured HCC cases from Jan 2000 to Dec 2008; all of these 126 cases received TAE as the initial therapy. Subsequently, 74 cases received staged surgical resection, and the remaining 52 cases underwent repeated TACE. The baseline demographic data, tumor characteristics, and long term survival were recorded and compared. Results: The demographic and baseline characteristics were comparable between the hepatic resection and TACE groups; furthermore, no significant difference in the tumor characteristics was detected between the two groups. The differences in in-hospital, 30-day and 90-day mortality between the two groups were not significant (P>0.05). However, the 1-, 3-, and 5-year overall survival rates were 85.1%, 63.5%, and 37.8%, respectively, in the hepatic resection group, which were significantly higher than those in the TACE group (69.2%, 46.2%, and 17.3%, respectively, P=0.004). Univariate and multivariate analyses indicated that these patients benefitted from hepatic resection compared with TACE with respect to long-term outcomes. Conclusions: Staged hepatic resection after TAE is an effective treatment that results in superior long-term survival to repeated TACE.

• Journal of Yeungnam Medical Science
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• v.17 no.2
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• pp.137-145
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• 2000

Background: Hepatocellular carcinomal(HCC) has been considered to be relatively radioresistant. The role of radiotherapy(RT) in the treatment of HCC is controversial. But RT has a role in the treatment of hepatocellular carcinoma as a single or combination modalities. The effect of radiotherapy on HCC was evaluated. Patients and Methods: From January 1984 through January 2000, a total of 18 patients with unresectable HCC underwent radiotherapy alone or in conjunction with transarterial embolization(TAE). We reviewed the medical ecords of patients treated with RT and measured the tumor size using measured the tumor size using planimetry method. The Kaplan-Meier method was used to calculate the survival rate. Results: The RT patients were 15 men and 3 women. The mean age was 51 years. four(22.2%) of them were accompanied with ascites. Eleven(61.1%) of them were accompanied with liver cirrhosis and their functions were 6, 3, 2 in each Child-Pugh A, B, C, respectively. A partial response(PR) was observed in 2 patients(11.1%), minimal response(MR) in 4 patients (22.2%) and no change(NC), in 11 patients(61.1%), whereas progressive disease(PD) was seen in 1 patients(6%), respectively. Conclusions: Although the radiotherapy in HCC did not improve the survival rate. it decreased the tmor size. Radiotherapy strengthens the therapeutic efficacy when combined with TAE, but more studies are needed.